共查询到20条相似文献,搜索用时 31 毫秒
1.
L. Felipe Pineda Claus Liebmann Sabine Hensellek Inge Paegelow Torsten Steinmetzer Andrea Schweinitz Jörg Stürzebecher Siegmund Reissmann 《Letters in Peptide Science》2000,7(2):69-77
A series of new non-peptide Bradykinin (BK)B2-receptor antagonists is reported. These newleads belong to a larger set including bothcommercially or otherwise available potentialcandidates found by proprietary database searchesusing 3D-pharmacophore models as query, and severalbis-benzamidino compounds selected from ourtryptase-like protease inhibitor library on thebasis of topological considerations, derived fromthe same models.Some of these compounds show functional competitiveantagonistic activity, inhibiting {in vitro} the BK-induced contraction of isolated guinea-pig ileum(GPI) and rat uterus with a pA2 up to 5.3 and7.0, respectively. They display also bindingaffinity (IC50 up to 0.56 M) to the BKB2-receptor in radioligand binding assays onGPI membrane preparations and on human IMR-90 fetallung fibroblast cells expressing this receptor subtype.Furthermore, the results with the commerciallyavailable compounds, in some cases developed astherapeutics, show that the used 3D-pharmacophoremodel allows to predict to some certainty possibleside actions of potential drugs. 相似文献
2.
L. Felipe Pineda Moises Hassan 《International journal of peptide research and therapeutics》1998,5(2-3):189-192
Summary In order to make a further contribution to the elucidation of the essential structural features for bradykinin (BK) antagonism,
we extracted 3D pharmacophore models from a training set consisting of nine relatively rigid, small organic, non-peptide molecules,
reported to be more or less active, competitive BK B2-receptor antagonists. This was accomplished by means of the expert system CatalystTM. The information contained in one of these models was then used to identify relevant structural features and perform consensus
molecular dynamics simulations including, in addition to the non-peptide antagonist set, four prototypical linear and cyclic
peptide antagonists, and BK itself. this combined approach allowed us to identify regions of the conformational space shared
by this series of compounds, which includes highly flexible, and, hence, otherwise almost inaccessible for conventional conformational
sampling techniques, peptide molecules. As a result, we obtained a relatively small number of extended pharmacophore models,
whose average, together with the original Catalyst model, could be used to search proprietary 3D databases for potential candidates.
The results of such a search are also reported. 相似文献
3.
In order to make a further contribution to the elucidation of the essential structural features for bradykinin (BK) antagonism, we extracted 3D pharmacophore models from a training set consisting of nine relatively rigid, small organic, non-peptide molecules, reported to be more or less active, competitive BK B2-receptor antagonists. This was accomplished by means of the expert system Catalyst. The information contained in one of these models was then used to identify relevant structural features and perform consensus molecular dynamics simulations including, in addition to the non-peptide antagonist set, four prototypical linear and cyclic peptide antagonists, and BK itself. This combined approach allowed us to identify regions of the conformational space shared by this series of compounds, which includes highly flexible, and, hence, otherwise almost inaccessible for conventional conformational sampling techniques, peptide molecules. As a result, we obtained a relatively small number of extended pharmacophore models, whose average, together with the original Catalyst model, could be used to search proprietary 3D databases for potential candidates. The results of such a search are also reported. 相似文献
4.
In the current study, the applicability and scope of 3D-QSAR models (CoMFA and CoMSIA) to complement virtual screening using
3D pharmacophore and molecular docking is examined and applied to identify potential hits against Mycobacterium tuberculosis Enoyl acyl carrier protein reductase (MtENR). Initially CoMFA and CoMSIA models were developed using series of structurally
related arylamides as MtENR inhibitors. Docking studies were employed to position the inhibitors into MtENR active site to
derive receptor based 3D-QSAR models. Both CoMFA and CoMSIA yielded significant cross validated q2 values of 0.663 and 0.639 and r2 values of 0.989 and 0.963, respectively. The statistically significant models were validated by a test set of eight compounds
with predictive r2 value of 0.882 and 0.875 for CoMFA and CoMSIA. The contour maps from 3D-QSAR models in combination with docked binding structures
help to better interpret the structure activity relationship. Integrated with CoMFA and CoMSIA predictive models structure
based (3D-pharmacophore and molecular docking) virtual screening have been employed to explore potential hits against MtENR.
A representative set of 20 compounds with high predicted IC50 values were sorted out in the present study. 相似文献
5.
Gupta S Fallarero A Järvinen P Karlsson D Johnson MS Vuorela PM Mohan CG 《Bioorganic & medicinal chemistry letters》2011,21(4):1105-1112
Dual binding site acetylcholinesterase (AChE) inhibitors are promising for the treatment of Alzheimer’s disease (AD). They alleviate the cognitive deficits and AD-modifying agents, by inhibiting the β-amyloid (Aβ) peptide aggregation, through binding to both the catalytic and peripheral anionic sites, the so called dual binding site of the AChE enzyme. In this Letter, chemical features based 3D-pharmacophore models were developed based on the eight potent and structurally diverse AChE inhibitors (I-VIII) obtained from high-throughput in vitro screening technique. The best 3D-pharmacophore model, Hypo1, consists of two hydrogen-bond acceptor lipid, one hydrophobe, and two hydrophobic aliphatic features obtained by Catalyst/HIPHOP algorithm adopted in Discovery studio program. Hypo1 was used as a 3D query in sequential virtual screening study to filter three small compound databases. Further, a total of nine compounds were selected and followed on in vitro analysis. Finally, we identified two leads—Specs1 (IC50 = 3.279 μM) and Spec2 (IC50 = 5.986 μM) dual binding site compounds from Specs database, having good AChE enzyme inhibitory activity. 相似文献
6.
Privitera PJ Beckstead RM Yates P Walgren R 《Cellular and molecular neurobiology》2003,23(4-5):805-815
1. The present study was undertaken to localize and characterize bradykinin (BK) binding sites in brains from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).2. Serial sections of brains were cut from adult WKY and SHR and specific [125I-Tyr0]bradykinin ([125I-Tyr0]BK) binding was determined using in vitro quantitative receptor autoradiographic techniques.3. Specific binding of [125I Tyr0]BK was localized in the medulla oblongata to the regions of the nucleus of the solitary tract (NTS), area postrema (AP), dorsal motor nucleus of the vagus (X), and caudal subnucleus of the spinal trigeminal nucleus in both strains of rat. The specific binding (85–90% of total binding) was of high affinity and saturable with K
D values in the range of 100 pM and a B
max of 0.75 fmol per mg tissue equivalent in the NTS–X–AP complex of both the WKY and SHR. In competition studies, the rank order of potencies was similar in both strains with BK = Lys-BK > icatibant >>> DesArg9-BK. The B2 receptor antagonist icatibant inhibited [125I-Tyr0]BK binding with a K
i value of 0.63 ± 0.19 nM in WKY and 0.91 ± 0.73 nM in SHR, while K
i values for the B>
1 receptor agonist DesArg9-BK were 1475 ± 1055 and 806 ± 362 nM in WKY and SHR, respectively.4. Our finding of specific high-affinity [125I-Tyr0]BK B2 binding sites in the NTS, AP, and the X of WKY and SHR is important because these brain areas are associated with central cardiovascular regulation. However, alterations in BK B2 receptors in the medulla that could contribute to the hypertensive state in the SHR were not detected. 相似文献
7.
Bradykinin (BK) and its analogs (1 nM-100 M) stimulated phosphoinositide (PI) turnover in murine fibrosarcoma (HSDM1C1) cells in a concentration-dependent manner. The relative potencies (EC50) were: BK=48±4 nM; Lys-BK=39±3 nM; Met-Lys-BK=158±33 nM; Des-Arg9-BK=2617±598 nM (means±SEM, n=3–14). All these analogs were full agonists and they produced up to 5.4±0.4-fold stimulation of PI turnover at the highest concentration (10–100 M) of the peptides. In contrast, the analogs [D-Arg0-HYP3-Thienyl5,8-D-Phe7]-BK (HYP3-antagonist), [D-Arg0-HYP3-Thienyl,5,8-D-Phe7]-BK (Thienyl antagonist) and Des-Arg9-Leu8-BK were inactive, as agonists, at 0.1 nM-1 M in this system. These data suggested that BK-induced PI turnover in these cells was mediated via B2-type of BK receptors. This was confirmed further by the fact that both the B2-selective Hyp3- and Thienyl-antagonists inhibited BK-induced PI turnover with KBS of 369±51 nM and 368±118 nM respectively while the B1-selective antagonist, Des-Arg9-Leu8-BK, was inactive at 1 M. [3H]BK receptor binding studies revealed two binding sites, one with high affinity (Kd=0.24±0.06 nM; Bmax=1.4±0.4 pmol/g tissue) and the other with low affinity (Kd=18.5±0.95 nM; Bmax=25.1±0.52 pmol/g tissue), on HSDM1C1 cell homogenates. The rank order of affinity of BK analogs at inhibiting specific [3H]BK binding was similar to that found for PI turnover. Taken together, these data have provided evidence for the presence of two B2-type BK binding sites on the HSDM1C1 cells. Based on the affinity parameters, the low-affinity component of [3H]BK binding in HSDM1C1 cells appears to be coupled to the phospholipase C-induced PI turnover mechanism. The high-affinity component has been previously shown to mediate the production of prostaglandins by activation of phospholipase A2. 相似文献
8.
Suzuki Y Kodama D Goto S Togari A 《Biochemical and biophysical research communications》2011,(2):317-321
Bradykinin (BK), a mediator of pain and inflammation, is involved in bone metabolism. We have previously reported that BK increased the synthesis of interleukin-6 and prostaglandin E2 via phosphorylation of ERK1/2 in human osteoblasts, SaM-1. In the present study, we investigated the signal transduction pathway of BK focusing on intracellular Ca2+ kinetics in SaM-1 cells. Bath-applied BK increased intracellular Ca2+ concentration through the activation of B2 receptors. Removal of extracellular Ca2+ attenuated the effects of BK. Additionally, thapsigargin, endoplasmic reticulum Ca2+ pump inhibitor, completely inhibited BK-induced increase of intracellular Ca2+. These results suggested that bath-applied BK activated store-operated Ca2+ channels (SOCCs) following Ca2+ store depletion via B2 receptor. Although the molecular components of SOCCs have yet to be conclusively identified in all cell types, recent studies demonstrated that transient receptor potential canonical (TRPC) channels are candidates for them. TRPC1, TRPC3, TRPC4 and TRPC6 were expressed in SaM-1 cells and inhibitors of TRP channel, 2-aminoethoxydiphenyl borate, GdCl3, LaCl3 and flufenamic acid, inhibited the effects of BK. These findings suggested that BK activated SOCCs and induced Ca2+ influx via B2 receptor in human osteoblasts. Molecular components of the SOCCs are suggested to be TRPC channels. 相似文献
9.
Two new tris-hydroxypyridinone based compounds (KEMPPr(3,4-HP)3 and KEMPBu(3,4-HP)3) have been developed and studied as strong sequestering agents for iron and the group III of metal ions, aimed as potential pharmacological applications on metal-chelation therapy. Their structure is based on the KEMP acid scaffold to which three 3-hydroxy-4-pyridinone chelating moieties are attached via two different size spacers. After the preparation and characterization of the compounds their physico-chemical properties were studied, in relation with their metal binding affinity and lipophilicity. The KEMPPr(3,4-HP)3 ligand was also bioassayed to evaluate its in vivo metal sequestering capacity from most organs using an animal model overload with 67Ga. These studies showed that, for both in solution and in vivo conditions, the compounds have higher metal chelating efficacy than Deferriprone, the commercially available iron chelator in medical application, thus some perspectives are envisaged as potential pharmaceutical drug candidates for chelating therapy. 相似文献
10.
基于作用于微管蛋白秋水仙碱结合位点的小分子抑制剂与生物靶标的复合晶体结构,采用分子模拟软件Discovery Studio 3.0的受体-配体药效团产生程序建立了系列3D药效团新模型(M1-M6),并用20个已知微管抑制剂验证了其可靠性.用新药效团模型对约10000个化合物的数据库进行了虚拟筛选,发现了一些潜在先导物.据此合成的二芳烃胺类新化合物20在抑制人白血细胞K562的初步实验中显示出了明显的细胞形态变化和抑制活性,对多种人癌细胞A549,KB,KBvin和DU145均有较强的抑制活性(GI500.17~1.02μmol/L),表明以此新构建的药效团模型进行理性设计和寻找新型抗癌先导物的方法具有一定的可行性. 相似文献
11.
J.D. Líbano-Soares 《生物化学与生物物理学报:生物膜》2008,1778(5):1316-1323
In a previous paper we showed that bradykinin (BK), interacting with its B2 receptor, inhibits proximal tubule Na+-ATPase activity but does not change (Na+ + K+)ATPase activity. The aim of this paper was to investigate the molecular mechanisms involved in B2-mediated modulation of proximal tubule Na+-ATPase by BK. To abolish B1 receptor-mediated effects, all experiments were carried out in the presence of (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu), des-Arg9-[Leu8]-BK (DALBK), a specific antagonist of B1 receptor. A dual effect on the Na+-ATPase activity through the B2 receptor was found: short incubation times (1-10 min) stimulate the enzyme activity; long incubation times (10-60 min) inhibit it. The stimulatory effect of BK is mediated by activation of phosphoinositide-specific phospholipase C β (PI-PLCβ)/protein kinase C (PKC); its inhibitory action is mediated by Ca2+-independent phospholipase A2 (iPLA2). Prior activation of the PI-PLCβ/PKC pathway is required to activate the iPLA2-mediated inhibitory phase. These results reveal a new mechanism by which BK can modulate renal sodium excretion: coupling between B2 receptor and activation of membrane-associated iPLA2. 相似文献
12.
Allosteric modulators for adenosine receptors may have potential therapeutic advantage over orthosteric ligands. Allosteric enhancers at the adenosine A1 receptor have been linked to antiarrhythmic and antilipolytic activity. They may also have therapeutic potential as analgesics and neuroprotective agents. A3 allosteric enhancers are postulated to be useful against ischemic conditions or as antitumor agents. In this review, we address recent developments regarding the medicinal chemistry of such compounds. Most efforts have been and are directed toward adenosine A1 and A3 receptors, whereas limited or no information is available for A2A and A2B receptors. We also discuss some findings, mostly receptor mutation studies, regarding localization of the allosteric binding sites on the receptors. 相似文献
13.
《Journal of receptor and signal transduction research》2013,33(5-6):531-553
AbstractThe binding of (3H)-estradiol (E2) to cytoplasmic estrogen receptors isolated from female rat hypothalamus-preoptic area by unlabeled estrogen and antiestrogens (nafoxidine and tamoxifen) was examined when the concentrations of both the agonist (3H)-E2) and unlabeled competitors were varied over a wide range. Concentrations of unlabeled E2 up to 10-10M decreased the affinity of the labeled steroid for its receptor; at higher E2 concentrations, the apparent number of binding sites (Bmax) began to decline. Thus at some concentrations, E2 may act as a mixed competitive and noncompetitive inhibitor of its own binding to hypothalamic cytosol receptors. The antiestrogens differed markedly from E2 in their interactions with hypothalamic estrogen receptors. Only at relatively high competitor concentrations (e.g., > 10-9M) did the antagonists appear to competitively inhibit (3H)-E2-receptor binding. The most striking observation was that tamoxifen and nafoxidine significantly inhibited (3H)-E2-receptor binding at very low competitor concentrations (e.g., 1 pM), but only slightly inhibited estrogen binding at intermediate concentrations (e.g., 10-10M). It was proposed that the non-linear, concentration-dependent effects of antiestrogens on the neural estrogen receptors might be due to complex interactions of the antagonists with a non-estrogen binding site. 相似文献
14.
R. Allin M. Mintz V. Russell A. Engelbrecht M. Lamm W. Daniels G. van der Spuy A. Jaffer L. Kellaway J. Taljaard 《Neurochemical research》1994,19(7):827-831
The effect of kindling on dopaminergic (DA) neurotransmission was assessed by measuring dopamine D1- and D2-receptor binding in the dorsal and ventral striatum of rats either 2 hours (short-term) or 3–4 weeks (long-term) after the last kindled seizure. Kindling did not have any significant long-term effect on DA D2-receptor Kd or Bmax values in the dorsal or ventral striatum or on DA D1-receptor parameters in the dorsal striatum. The short-term effect of kindled seizures was to abolish the asymmetry in DA D2-receptor density observed in the dorsal striatum of control rats. DA D1-receptor density was also increased in the dorsal striatum contralateral to the kindled amygdala of short-term rats. The short-term effects support the notion that limbic seizures can modify the lateral imbalance of DA activity in the striatum. 相似文献
15.
Haffemayer B Richard E Mattras H Marie J 《Biochemical and biophysical research communications》2008,366(4):1001-1006
Pro258 in transmembrane domain (TMD) 6 of the bradykinin (BK) B2 receptor (B2R) is highly conserved among G-protein coupled receptors (GPCRs). Using mutagenesis, we show that Pro258 is required for normal trafficking of the receptor to the plasma membrane and that mutation of Pro258 to Ala or Leu but not Gly, enhances BK efficacy to induce receptor activation. Furthermore, P258A mutation suppresses the constitutive activity of a constitutively activated N113A-B2R mutant but preserves the antagonist to agonist efficacy shift previously observed on the N113A single mutant. Our data suggest that Pro258 in TMD6 is required for agonist-independent activation of the B2R and that straightening of TMD6 at the Pro-kink might favor G-protein coupling. It is also shown that Asn113 is a contact point of BK interaction and it is proposed that the release of a TMD3-TMD6 interaction involving Asn113 is crucial for the efficacy shift from antagonism toward agonism. 相似文献
16.
《Life sciences》1992,50(7):PL47-PL52
The responses of the rat isolated stomach fundus to bradykinin (BK) and des-Arg9-BK (DA-BK) have been examined. In rat isolated stomach fundus pre-contracted with BaCl2 (0.5-1 mM), BK caused concentration-dependent biphasic responses characterized by relaxation followed by contraction. DA-BK also caused marked relaxations, but, unlike BK, induced only small contractions. Removal of the mucosal layer initially abolished the relaxant responses to BK and both responses to DA-BK without affecting BK-induced contractions, but repeated challenges with BK or DA-BK revealed a time-depeendent reappearance of the relaxant responses, suggesting “de novo” synthesis of BK receptors. Pretreatment of rat stomach fundus with tetrodotoxin (1 μM), atropine (1 μM), captopril (3 μM), prazosin (1 μM) or glibenclamide (1 μM) did not significantly modify the biphasic responses to BK (300 nM). The biphasic responses to DA-BK were antagonized selectivley by the B1 receptor antagonist des-Arg9-[Leu 8]-BK (DAL- BK) (1 μM). In contrast, the biphasic responses to BK were unaffected by DAL-BK or by several selective peptide antagonists of B2 receptors including NPC 431 (Thi5,8, D-Phe7)-BK, NPC 349 (D-Arg Hyp3, Thi5,8, D-Phe7)-BK, NPC 567 (D-Arg -Hyp3, D-Phe7)-BK and NPC 361 (D-Phe7)-BK (3 to 10 μM). These results are consistent with the view that the biphasic responses of the rat isolated stomach fundus to BK appear to be mediated by a novel BK receptor which is insensitive to blockade by B1 and B2 selective BK receptor antagonists. 相似文献
17.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1997,1355(1):89-98
A cDNA encoding a mouse B2 bradykinin (BK) receptor was stably transfected in Chinese hamster ovary (CHO) cells. In two resulting transformants, mouse B2 BK receptor was found to induce a twofold elevation in the inositol-1,4,5-trisphosphate level. In a pertussis toxin-insensitive manner, BK also produced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i). The initial elevation in [Ca2+]i was abolished by thapsigargin pretreatment in Ca2+-free medium. The second phase was dependent on external Ca2+. The BK/inositol trisphosphate- and thapsigargin-sensitive Ca2+ stores required extracellular Ca2+ for refilling. Ca2+ influx induced by BK and thapsigargin was confirmed by Mn2+ entry through Ca2+ influx pathways producing Mn2+ quenching. Genistein, a tyrosine kinase inhibitor, partially decreased the BK-induced [Ca2+]i increase during the sustained phase and the rate of Mn2+ entry. BK had essentially no effect on the intracellular cyclic AMP level. The results suggest that the mouse B2 BK receptor couples to phospholipase C in CHO cells and that its activation results in biphasic [Ca2+]i increases, by mobilization of intracellular Ca2+ and store-depletion-mediated Ca2+ influx, the latter of which is tyrosine phosphorylation-dependent. 相似文献
18.
The bradykinin (BK) B1 receptor (B1R) is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP) (enhanced green FP [EGFP] or mCherry) prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively). The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy). Both assays indicated that the best design was FP-(Asn-Gly)n-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly)15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology). 相似文献
19.
With the aim of finding new adenosine receptor (AR) ligands presenting the 3-amidocoumarin scaffold, a study focusing on the discovery of new chemical entities was carried out. The synthesized compounds 1–8 were evaluated in radioligand binding (A1, A2A and A3) and adenylyl cyclase activity (A2B) assays in order to determine their affinity for human AR subtypes. The 3-benzamide derivative 4 showed the highest affinity of the whole series and was more than 30-fold selective for the A3 AR (Ki = 3.24 μM). The current study supported that small structural changes in this scaffold allowed modulating the affinity resulting in novel promising classes of A1, A2A, and/or A3 AR ligands. We also performed docking calculations in hA2A and hA3 to identify the hypothetical binding mode for the most active compounds. In addition, some ADME properties were calculated in order to better understand the potential of these compounds as drug candidates. 相似文献
20.
Diego F. Hernández-Ramírez Elizabeth Olivares-Martínez Carlos A. Núñez-Álvarez Eneas A. Chavelas Enrique García-Hernández Gregoria Gómez-Hernández Luis Llorente Antonio R. Cabral 《Biochemical and biophysical research communications》2014
Several studies have shown that conformational changes of β2-glycoprotein I (β2GPI) when bound to negatively charged components expose cryptic epitopes and subsequent binding of anti-β2GPI from patients with antiphospholipid syndrome (APS). However, the role of the carbohydrate chains of β2GPI in this anti-β2GPI reactivity is poorly understood. We therefore studied the reactivity and inhibition of anti-β2GPI antibodies from APS patients with native, partially glycosylated β2GPI (pdβ2GPI; without sialic acid) and completely deglycosylated β2GPI (cdβ2GPI). To determine the potential biologic importance of these glycoforms and their interaction with anti-β2GPI in vitro, stimulation assays were performed with the U937 cell line. Circular dichroism (CD) and fluorescence analysis of the three β2GPI forms were also studied. We found an increased reactivity of anti-β2GPI against pdβ2GPI and cdβ2GPI compared to native β2GPI. Both deglycosylated β2GPI isoforms showed higher inhibition of the anti-β2GPI reactivity than the native protein in soluble-phase. Likewise, the antibody/β2GPI/glycoform complexes increased the synthesis of IL-6, IFNγ and TNFα and the expression of HLA-DR, CD14 and CD11c in U937 cells. CD and fluorescence studies of the glycoforms yielded considerable changes in the fluorescence signals. Our work suggests that the partial or complete removal of the carbohydrate chains uncover cryptic epitopes present in β2GPI. The differentiation and increased synthesis of pro-inflammatory cytokines by U937 cells in vitro may have pathogenetic implications. 相似文献